The long-term objective of the overall proposal program is to develop clinically-usable non-invasive microwave poration instrumentation to increase the uptake and retention of chemotherapeutic agents by targeted malignant cells thereby significantly enhancing the anti-cancer activity of these agents. The proposed instrumentation consists of high-peak-power pulsed microwave generators whose output is directed by non-invasive applicators to the tumor site under treatment where high electric fields are developed at low average power levels that do not cause appreciable temperature increases in the exposed tissues. During a preliminary pilot study using 20 Copenhagen rats, it was demonstrated that microwave pulsing could sharply increase the uptake of systemically circulating fluorescin Dextran (10,000 daltons molecular weight) by implanted AT2 malignant prostate tumors. There was no significant uptake of Dextran by healthy cells that were pulsed indicating that a large therapeutic advantage can be obtained by microwave pulsing. This preliminary study also indicated that remission of tumors could be obtained by combining microwave pulsing and systemically administered Taxol. During the proposed Phase I program, microwave instrumentation and treatment protocols will be optimized using Copenhagen rats with implanted AT2 prostate tumors, and the design of instrumentation and treatment protocols for future clinical trials will be considered. PROPOSED COMMERCIAL APPLICATION: Cancer treatment: (1) Smaller doses of chemotherapeutic drugs, thus reducing systemic toxicity. (2) The therapeutic use of monoclonal antibodies, radioactive nuclei, and genes would be facilitated by the increased porosity of the targeted cell membranes. Gene therapy not only for cancer, but also for diseases ranging from cystic fibrosis to AIDS.